Cruzain is an essential cysteine protease of Trypanosoma cruzi and a therapeutic target for Chagas' disease. Eight dogs were infected with T. cruzi; three were treated with an inhibitor of cruzain, K777, for 14 days. Treatment with K777 abrogated myocardial damage by T. cruzi, as documented by histopathological lesion scores and serum troponin I levels.
Acidification should replace NaF alone as the recommended method for obtaining an accurate glucose concentration. Diagnostic cut points based on blood samples collected into tubes containing NaF as the only inhibitor of glycolysis are likely to be too low.
Amyloidosis is a complication of long-term hemodialysis treatment. The major histological feature of hemodialysis-associated amyloidosis (HAA) is the deposition of amyloid fibrils in the affected lesions, due, in part, to elevated serum beta2-microglobulin (beta2M) levels. In vitro studies reveal that serum immunoglobulin light and heavy chains co-deposit with beta2M in tissues affected by HAA. Only one study of HAA has been performed in young dialysis patients. We therefore assessed risk factors for HAA in a group (n=30) of young (18.7+/-0.9 years) patients receiving chronic, uninterrupted hemodialysis using cellulose acetate membranes. All patients initiated dialysis before reaching 18 years of age. The pre-dialysis serum beta2M level was 49.7+/-3.9 mg/l (normal 0-2.4 mg/l). Since serum albumin was normal (4.3+/-0.1 mg/dl) and serum protein/albumin was elevated (1.7+/-0.0, normal 1.2-1.5), indicating increased circulating protein, we assayed immunoglobulins in the same patients. The serum immunoglobulin levels (expressed as a percentage of the total level of serum proteins) were elevated (21.3+/-0.9%, normal 11.1%-21.0%). The Kt/v was 1.37+/-0.03, suggesting that the high levels of serum beta2M and immunoglobulins were not due to inadequate dialysis in these patients. Patients with residual renal function (Kr) did display significantly lower serum levels of beta2M (33.2+/-2.3, P=0.03). Furthermore, improved clearance of beta2M correlated with higher values of Kr (r=0.914). In contrast, serum levels of immunoglobulin (22.6+/-3.7, P=0.5) were unaffected by Kr. In addition, there was no correlation between older age at onset of dialysis and serum levels of either beta2M (r=0.107) or immunoglobulins (r=0.321). Finally, the length of time on dialysis had no effect on serum levels of either beta2M (r=0.105) or immunoglobulins (r=0.092). Taken together, these results indicate that young hemodialysis patients may be at risk for HAA.
Serum levels of parathyroid hormone (PTH), alkaline phosphatase (AP), and calcium (Ca2+) have been used to evaluate renal osteodystrophy (RO) in adult patients undergoing dialysis. Osteocalcin (BGP) is a bone protein which also serves as a marker for bone turnover. Serum BGP levels correlate positively with rates of bone turnover and serum concentrations of PTH, AP, and Ca2+ in various studies of adult end-stage renal disease (ESRD) patients, whereas other studies reveal BGP to be a poor indicator of bone turnover in ESRD. RO is a significant problem in pediatric ESRD patients; however, there have been few studies evaluating the correlation of markers for RO in children with ESRD. We measured serum PTH, AP, Ca2+, and BGP levels in a group (n=23) of pediatric patients with ESRD and assessed the correlation among the markers. There was a positive correlation between serum PTH and AP (r=0.658, p<0.001). In contrast, there was no correlation between either serum Ca2+ or BGP, and either PTH or AP. The correlation between Ca2+, BGP and either PTH or AP was unaffected by growth in our patient population. Finally, neither age nor pubertal stage improved the correlation between either Ca2+ or BGP, and either PTH or AP. We conclude that serum PTH and AP are useful markers for RO, whereas calcium and BGP levels should not be used to evaluate RO in pediatric ESRD patients.
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